Aujeszky's disease is a serious and often fatal respiratory and nervous system disease in swine, occurring worldwide. Young pigs are its major victims, but adults are susceptible and are also latent carriers of the virus, which can be passed to piglets. The disease is rare but usually fatal in sheep, goats, cattle, cats, and dogs.
The disease is caused by pseudorabies virus (PrV), also known as Herpesvirus suis. PrV consists of a linear, double stranded, 9.times.10.sup.7 dalton molecule of DNA in a capsid surrounded by an envelope containing surface glycoproteins. The coding capacity of the PrV genome is 100 to 200 genes.
Current vaccines consist of inactivated or attenuated PrV; these reduce mortality but do not prevent latent infection. In theory, subunit vaccines, which would generally contain only immunogenic surface proteins of the virus, would be safer but perhaps not as effective. Protection against and recovery from infection by various pathogenic agents is determined by the host's immunological system. There are two interrelated but distinct immunological responses: humoral immunity, which is provided by circulating antibodies; and cellular immunity, provided by certain cells of the lymphoid system. Purified antigens alone, as in subunit vaccines, are sufficient to stimulate an antibody response in most cases; but they may not stimulate the cellular immune response which plays an equally or possibly more important role in prevention or recovery from infection. Live vaccines are the most effective means of stimulating both immunological responses. A need exists for live vaccine for PrV.
Vaccinia virus has been used in the worldwide eradication of smallpox. Its effectiveness in the vaccination program is due to its relative safety, stability, ease of administration and low cost. Vaccinia virus, a DNA virus, has several advantageous characteristics for use as a vector for creating live recombinant vaccines: they permit relatively easy genetic manipulation; they have a genome which can accept a large amount of foreign DNA; they are not oncogenic, are easy to grow and purify, and they have an extremely wide host range, infecting both man and animals.
Paoletti et al. (U.S. Pat. No. 4,603,112) have developed a technique known as in vivo recombination for integration of foreign DNA into vaccinia virus. Several foreign genes can be recombined into one virus using this technique, but each gene must be inserted individually.
A means of utilizing vaccinia virus as a eukaryotic vector has recently been developed. It has been demonstrated that foreign DNA sequences can be inserted into the genome of vaccinia virus by a process of site specific homologous recombination between replicating vacccinia genomes and appropriate vaccinia DNA sequences which flank the foreign DNA of interest (Panicali et al., Proc. Natl. Acad. Sci. USA. 1982. Vol. 79, pgs. 4927-4931). Recombinant viruses have been created in this manner to contain and express DNA sequences which code for proteins of pathogenic organisms.